U.S. Pat. No. 4,705,797 incorporated by reference herein discloses novel asymmetric diesters of 1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylic acid, stereochemically isomeric forms and pharmaceutically acceptable salts thereof. These compounds are antihypertensive agents. Among them lercanidipine, chemically 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[(3,3-diphenylpropyl) methylamino]-1,1-dimethylethyl methyl ester is an antagonist of type-L calcium channels, and has been found to be very active as an antihypertensive and as an agent for the treatment of angina and coronary disease. Lercanidipine is represented by the following structure:

Processes for the preparations of Lercanidipine and related compounds were disclosed in U.S. Pat. No. 4,705,797 and WO 96/35668 A1 incorporated by reference herein.
According to U.S. Pat. No. 4,705,797, 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol is esterified with diketene to form 1,1,N-trimethyl-N-(3,3-diphenylpropyl)-2-amino-2-propanol, which is then coupled with 3-nitrobenzaldehyde to give 1,1,N-trimethyl-N-(3,3-diphenylpropyl)-2-aminoethyl α-acetyl-3-nitrocinnamate, followed by cyclization with methyl 3-aminocrotonate in refluxing isopropanol to give lercanidipine hydrochloride hemihydrate. The yield of lercanidipine obtained according to the process described in U.S. Pat. No. 4,705,797 is poor and the process involves column chromatographic purifications. Methods involving column chromatographic purifications cannot be used for large-scale operations, thereby making the process commercially not viable.
According to WO 96/35668, 2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid is halogenated with a halogenating agent in an aprotic solvent, followed by treatment with 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol in an aprotic solvent and isolating the resultant lercanidipine as its anhydrous hydrochloride. This process involves direct condensation of 2,N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol with 2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydro-pyridine-3-carbonyl chloride.
The reaction requires longer time to complete and the yield obtained is not satisfactory.
The present invention is an improved, commercially viable process solving the aforesaid problems associated with processes described in the prior art.
The object of the present invention is to provide a process for preparing lercanidipine and pharmaceutically acceptable acid addition salts of lercanidipine, and solvates and hydrates thereof in high purity and in high yield using novel intermediates in lesser reaction time.